BACKGROUND: Hypoalbuminemia is a powerful predictor of cardiovascular mortality in maintenance hemodialysis patients. Increased biomarkers of acute-phase inflammation and oxidative stress are highly prevalent and also correlate with cardiovascular morbidity and mortality. The extent to which hypoalbuminemia, biomarkers of inflammation, and biomarkers of oxidative stress are linked in this patient population is unknown. We hypothesized that a high proportion of hypoalbuminemic hemodialysis patients also would manifest increased levels of biomarkers of inflammation and oxidative stress. METHODS: We surveyed 600 maintenance hemodialysis patients and identified 18 severely hypoalbuminemic patients (serum albumin level < 3.2 g/dL [32 g/L]) without recent infection or hospitalization. We then identified 18 age-, race-, sex-, and diabetes-matched normoalbuminemic hemodialysis patients, as well as 18 age-, race-, sex-, and diabetes-matched healthy subjects, for cohort comparison. Measurements of plasma interleukin-6 (IL-6) levels, plasma protein reduced thiol content, plasma protein carbonyl content, and plasma free F(2)-isoprostane levels, as well as serum concentrations of C-reactive protein (CRP) and prealbumin, were performed for study purposes. RESULTS: Levels of serum CRP, IL-6, plasma protein thiol oxidation, and protein carbonyl formation were significantly elevated in both hypoalbuminemic and normoalbuminemic hemodialysis patients compared with healthy subjects and also were significantly different in hypoalbuminemic maintenance dialysis patients compared with normoalbuminemic hemodialysis patients. Prealbumin levels were significantly lower in hypoalbuminemic hemodialysis patients than in other groups. CONCLUSION: There is a high prevalence of inflammation and oxidative stress in the maintenance hemodialysis population. Levels of inflammatory and oxidative stress biomarkers are increased further in hypoalbuminemic compared with normoalbuminemic dialysis patients. Hypoalbuminemia, acute-phase inflammation, and oxidative stress may act synergistically to increase cardiovascular morbidity and mortality risk in maintenance hemodialysis patients.